Long-term efficacy of deferasirox in preventing cardiovascular complications in the iron-overloaded gerbil.

Iron-induced cardiovascular disease is the leading cause of death in iron-overloaded patients. Deferasirox is a novel tridentate oral chelator that exhibits a half-life suitable for once-daily dosing; however, little is known regarding the effectiveness of this agent in preventing iron-induced cardiovascular disease. Adult male Mongolian gerbils were randomly divided into 3 groups: control, iron overload, and iron overload followed by deferasirox treatment. Iron-overloaded animals received iron dextran 100 mg/kg intraperitoneally (ip)/5 days for 10 weeks, while deferasirox was given 100 mg/kg per d orally (po) for 9 months post iron loading. Cardiac and aortic iron levels were determined by inductively coupled plasma atomic emission spectrometry. Gerbil electro- and echocardiograms were obtained in anesthetized animals at regular intervals. Compared to control animals, iron concentration was 3.3- and 2.4-fold higher in iron-overloaded heart and aorta, respectively (P < .05). Deferasirox treatment reduced cardiac and aortic iron levels by 32% and 35%, respectively (P < .05). These results were consistent with the decrease in cellular iron deposition observed with Prussian Blue iron staining. Iron-overloaded gerbils were found to exhibit frequent arrhythmias including premature ventricular contractions, supraventricular tachycardia, and recurrent ventricular tachycardia. In addition, echocardiographic assessment demonstrated iron overload-associated increase in left ventricular dimensions including left ventricular posterior wall dimension (LVPWd: 49%), left ventricular internal dimension (LVIDd: 26%), and left ventricular septum thickness (LVSd: 42%). These parameters were significantly reduced with deferasirox treatment (LVPWd: 23%, LVIDd: 24%, and LVSd: 27%). Iron overload was also associated with reduced ejection fraction (EF: by 30%) and fractional shortening (FS: by 23%) in comparison with controls (P < .05). With deferasirox treatment, these values were higher (EF: by 30%, FS: by 28%) compared to iron-overloaded group. These findings suggest that deferasirox may be useful for attenuating iron-induced changes in cardiac structure and function.

Deferasirox protects against iron-induced hepatic injury in Mongolian gerbil.

Iron overload is associated with an increased risk of liver complications including fibrosis, cirrhosis, and hepatocellular carcinoma. Deferasirox is a new oral chelator with high iron-binding potency and selectivity. Here we investigate the ability of deferasirox to remove excessive hepatic iron and prevent iron-induced hepatic injury. Adult male Mongolian gerbils were divided into 3 groups (n=5/group)-control, iron overload (100 mg iron-dextran/kg body weight/5 days; intraperitoneal for 10 weeks), and iron overload followed by deferasirox treatment (100 mg deferasirox/kg body weight/d; pulse oral for 1 or 3 months). Compared with the nontreated iron overload group, deferasirox reduced hepatic iron concentration by 44% after 3 months of treatment (P<0.05). Histological analysis of hepatic tissue from the iron overloaded group detected frequent iron deposition, evidence of hepatic damage, and an accumulation of lipid vacuoles. Iron deposition was significantly diminished with deferasirox treatment, and no evidence of lipid accumulation was observed. Immunoblotting demonstrated that iron overload caused approximately 2-fold increase in hepatic ferritin expression (P<0.05), which was 48% lower after 3 months of deferasirox treatment (P<0.05). Deferasirox treatment also was associated with reduced hepatic protein oxidation, superoxide abundance, and cell death. The percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells in the deferasirox-treated livers was 41% lower than that of iron overloaded group (P<0.05). Similarly, an iron-related increase in the expression of Bax/Bcl2, Bad, and caspase-3 were significantly lower after deferasirox treatment. These findings suggest that deferasirox may confer protection against iron-induced hepatic toxicity.

Global education implications of the foreign pharmacy graduate equivalency examination.

Although the Foreign Pharmacy Graduate Equivalency Examination (FPGEE) is not intended to measure educational outcomes or institutional effectiveness, it may be a reliable and valid criterion to assess the quality or success of international pharmacy programs. This comprehensive review describes the evolution and historical milestones of the FPGEE, along with trends in structure, administration, and passing rates, and the impact of country of origin on participant performance. Similarities between the FPGEE and the Pharmacy Curriculum Outcomes Assessment (PCOA) are also explored. This paper aims to provide a global prospective and insight for foreign academic institutions into parameters for evaluating their students' educational capabilities.

Physician attitudes toward collaborative agreements with pharmacists and their expectations of community pharmacists' responsibilities in West Virginia.

OBJECTIVES: To (1) investigate physicians' expectations about community pharmacist's roles and physician attitudes toward collaborative agreements with community pharmacists in West Virginia and (2) determine physicians' perceptions of pharmacists providing medication therapy management (MTM) services. METHODS: A mail survey was conducted for a random sample of 500 physicians practicing in West Virginia. Survey items measured the physicians' perceptions about the roles of pharmacists, their level of comfort with pharmacists providing certain MTM services, and their attitudes toward a collaborative agreement with pharmacists. RESULTS: 102 responses were received, yielding a response rate of 22.1%; 60% of the physicians had a favorable attitude toward supporting collaborative agreement with pharmacists. Physicians were more comfortable with certain areas of MTM services, such as general drug education and the Medicare Part D prescription drug benefit, and they expected pharmacists to identify medication errors and educate the patients about the safe and appropriate use of medications. CONCLUSION: Of the physician respondents, 60% reported a favorable attitude toward collaborative practice agreements, but their attitude toward pharmacists' role in collaborative drug therapy management and pharmacists providing MTM services were not that favorable. Participating physicians may not have consistent expectations regarding pharmacists providing patient care.

Deferasirox removes cardiac iron and attenuates oxidative stress in the iron-overloaded gerbil.

Iron-induced cardiovascular disease is the leading cause of death in iron-overloaded patients. Deferasirox is a novel, once daily oral iron chelator that was recently approved for the treatment of transfusional iron overload. Here, we investigate whether deferasirox is capable of removing cardiac iron and improving iron-induced pathogenesis of the heart using the iron overload gerbil model. Animals were randomly divided into three groups: control, iron overload, and iron overload + deferasirox treatment. Iron-dextran was given 100 mg/kg per 5 days i.p for 10 weeks. Deferasirox treatment was taken post iron loading and was given at 100 mg/kg/day p.o for 1 or 3 months. Cardiac iron concentration was determined by inductively coupled plasma atomic emission spectroscopy. Compared with the untreated group, deferasirox treatment for 1 and 3 months decreased cardiac iron concentration 17.1% (P = 0.159) and 23.5% (P < 0.05), respectively. These treatment-associated reductions in cardiac iron were paralleled by decreases in tissue ferritin expression of 20% and 38% at 1 and 3 months, respectively (P < 0.05). Using oxyblot analysis and hydroethidine fluorescence, we showed that deferasirox significantly reduces cardiac protein oxidation and superoxide abundance by 36 and 47.1%, respectively (P < 0.05). Iron-induced increase in oxidative stress was also associated with increased phosphorylation of ERK-, p38-, and JNK-mitogen-activated protein kinase (MAPK). Interestingly, deferasirox treatment significantly diminished the phosphorylation of all three MAPK subfamilies. These results suggest that deferasirox may confer a cardioprotective effect against iron induced injury.